Excessive collagen deposition in the skin is a hallmark of scleroderma. Currently there are no safe and/or[unreadable] effective therapies. Excessive accumulation of collagen is responsible for the markedly thickened and hard[unreadable] feel to the involved skin of scleroderma. Therefore, a therapy that can safely enhance collagen breakdown[unreadable] is expected to improve it. We have accumulated solid evidence that UV irradiation of human skin activates a[unreadable] complex signaling cascade in cells that ultimately results in a several fold increase in the amount of matrix[unreadable] metalloproteinases (MMPs) with consequent degradation of collagen, while simultaneously inhibiting new[unreadable] procollagen synthesis. Thus, by removing already present dermal collagen and suppressing production of[unreadable] new collagen, UV is capable of causing a net collagen loss in human skin. As a phototherapeutic device[unreadable] however, both UVB (290-320nm) and UVA1 (340-400nm) have significant limitations. More energetic UVB[unreadable] is associated with sunburn reaction, and its carcinogenic potential is well established. UVA1 is safer and[unreadable] better tolerated by human skin. However, we have learned that both natural and UV-induced skin[unreadable] pigmentation are effective blockers of UVA1. Scleroderma affects subjects with all levels of skin[unreadable] pigmentation (types I-VI). An antifibrotic treatment modality that is not influenced by skin color will offer a[unreadable] significant medical advancement, especially in darkly pigmented African American, Hispanic, Indian, or Asian[unreadable] patients (types V&VI). Our preliminary data indicate that infrared irradiation (IR; specifically 700-4,000nm)[unreadable] that raises skin surface temperature to 41 degrees C is capable of safely inducing MMPs and inhibiting procollagen[unreadable] irrespective of human skin pigmentation. Thus we hypothesize that IR will also improve scleroderma and[unreadable] other fibrotic diseases. We propose to 1) fully characterize the ability of IR to reduce collagen in normal skin,[unreadable] and 2) obtain preliminary data of the IR effect on scleroderma skin. The data generated with the assistance[unreadable] of RDCC will form the basis for an application to the NIH to fund a multicenter IR therapeutic trial in[unreadable] scleroderma.